The basic aims of this research grant are twofold: 1) to evaluate the effect of transmucosal volume flows (absorption and secretion) on the various capillary and interstitial forces (tissue fluid pressure, interstitial oncotic pressure, plasma oncotic pressure, capillary pressure and lymph flow) that govern transcapillary fluid exchange in the small intestine and 2) to determine the permeability characteristics of the intestinal microcirculation. The addition of fluid (absorption) into or removal of fluid (secretion) from the mucosal interstitium via solute coupled mucosal transport should alter interstitial volume and forces, thereby altering transcapillary and lymphatic volume flows. Likewise, if excessive fluid accumulates in the interstitium as a result of alterations in capillary filtration forces, interstitial volume and fluid pressure will increase and can ultimately result in a net fluid movement into the intestinal lumen. An altered capillary permeability will also greatly influence fluid movement between the mucosal interstitium and capillary lumen and therefore, is a major determinant of the hydration state of the mucosal interstitium. We propose to study the effects of volume flows on capillary, tissue, and lymphatic forces and flows in isolated autoperfused intestinal loops during net volume secretion induced by various agents (humoral and pharmacological) and physiological maneuvers (plasma dilution, venous pressure elevation). Capillary permeability will be assessed using a lymphatic protein flux approach recently developed in our laboratory in which the flux of various plasma proteins of known molecular size are measured using lymph protein concentration and lymph flow as a measure of capillary protein flux. From the information obtained in these studies, we can build a comprehensive model of how the various forces governing transcapillary fluid exchange are related to intestinal volume transport, and whether humoral and pharmacological agents affect volume transport directly by increasing solute transport, or indirectly by altering intestinal, capillary and/or lymphatic dynamics.